A recent report from the Radiological Physics Center (RPC) revealed that 38% of institutions failed the head- and-neck IMRT phantom credentialing test at the first attempt. A wide variety of causes for failure were identified. The report provides evidence that IMRT implementation is non-trivial and prone to error, and that patient treatment may be compromised as a result. A truly practical 3D dosimetry system would address a root cause of these failures, by enabling comprehensive dosimetric verification during commissioning and routine QA. This proposal will further develop a clinically viable 3D dosimetry system and conduct the first comprehensive 3D investigations of the accuracy of dosimetry in IMRT delivery, in patient cohorts. Our prior research has demonstrated that a new PRESAGE/optical-CT system can perform accurate and high- resolution 3D dosimetry, and has critical advantages over alternative approaches. These include substantially greater accuracy, lower noise, elimination of major sources of artifacts (scatter and edge effects), and improved practicality (robustness to lab/clinical environment, stability, machineability etc). These advantages render the PRESAGE/Optical-CT system a viable 3D dosimetry system for the future. We propose a strong 3- party consortium to pursue two major aims; a continued technical and investigational aim, and a new clinical applications aim. The consortium combines outstanding expertise in 3D dosimetry (Duke) with credentialing experience (RPC), and materials expertise (Rider). The aims balance investigating innovations to facilitate 3D dosimetry for the non-specialized clinic, while still addressing the urgent need for detailed clinical IMRT dosimetry studies using a more specialized system. We hypothesize novel optical-CT scanning systems, and novel radiochromic formulations will achieve substantial increase in speed and practicality without compromising accuracy. We also hypothesize that 3D dosimetry techniques will detect more clinical IMRT deliveries failing standard comparison metrics, than conventional 2D techniques. This proposal will conduct the first comprehensive 3D investigations of the accuracy of IMRT deliveries in cohorts of patients in key clinical sites (pelvic, head-and-neck, and thorax). Successful completion will elevate the state-of-the-art for verification of advanced radiation treatments, and may demonstrate the feasibility of a powerful and comprehensive new 3D credentialing technology with potential to elevate the standard of practice in clinical trials. There is an urgent need to improve the accuracy of advanced radiation therapy. We investigate a 3- dimensional dosimetry system that will address this need by facilitating dosimetric error detection. The first comprehensive investigations of the accuracy of dosimetry in patient treatments in 3D will be conducted. [unreadable] [unreadable] [unreadable]